Disarming oxidized lipids: AAV-delivered antibody neutralization as an emerging strategy against ALS

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disease affecting motor neurons (MNs) and the neuromuscular axis. Despite decades of research on its molecular trigger and pathological mechanisms, and the search for effective disease-modifying therapies, both questions remain largely unknown. A common feature of ALS, present in 97% of cases, is the mislocalization, aggregation, and functional disruption of TAR DNA-binding protein 43 (TDP-43),1 yet the upstream trigger of this proteinopathy is poorly understood.